Zhao Biwei, Ricciardi Robert P
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Levy Research Building, Room 221, 4010 Locust Street, Philadelphia, PA 19104, USA.
Virology. 2006 Sep 1;352(2):338-44. doi: 10.1016/j.virol.2006.04.036. Epub 2006 Jun 15.
In adenovirus-12 tumorigenic cells, the viral E1A-12 protein mediates transcriptional down-regulation of the major histocompatibility complex (MHC) class I genes by targeting the class I enhancer. Here, we demonstrate by a combination of antisense and chromatin immunoprecipitation (ChIP) analysis that E1A-12 is a physical component of the class I enhancer repression complex, known to comprise COUP-TFII and histone deacetylase 1 (HDAC1). Significantly, E1A antisense was shown to co-eliminate E1A-12 as well as HDAC1 and HDAC8, but not HDAC3, from the enhancer repression complex. Consistent with elimination of HDAC1 and HDAC8, E1A antisense also resulted in a dramatic increase in histone acetylation, a hallmark of transcriptionally active chromatin. Importantly, MHC class I antigen expression was restored on the surface of E1A antisense-transfected cells. These results demonstrate that E1A-12 is associated with the MHC class I complex and apparently mediates class I transcriptional down-regulation by enacting chromatin repression through HDAC1 and HDAC8.
在腺病毒12致瘤细胞中，病毒E1A - 12蛋白通过作用于I类增强子介导主要组织相容性复合体（MHC）I类基因的转录下调。在此，我们通过反义技术与染色质免疫沉淀（ChIP）分析相结合的方法证明，E1A - 12是I类增强子抑制复合物的一个物理组成成分，已知该复合物包含COUP - TFII和组蛋白去乙酰化酶1（HDAC1）。值得注意的是，反义E1A被证明可从增强子抑制复合物中共同去除E1A - 12以及HDAC1和HDAC8，但不能去除HDAC3。与HDAC1和HDAC8的去除相一致，反义E1A还导致组蛋白乙酰化显著增加，这是转录活性染色质的一个标志。重要的是，在反义E1A转染细胞的表面恢复了MHC I类抗原的表达。这些结果表明，E1A - 12与MHC I类复合物相关，并且显然通过HDAC1和HDAC8实施染色质抑制来介导I类转录下调。
